Hemophilia A: Gene Therapy
Overview: Hemophilia A is the most common severe hereditary bleeding disorder and affects roughly 1 in 7,500 males2. This disease is brought about by a mutation in the gene that produces a protein called Factor VIII. Factor VIII is a protein involved in the blood clotting cascade, without which, blood clotting can’t properly take place. Patients suffering from Hemophilia A do not have enough Factor VIII circulating in their blood plasma, which means if they receive the slightest trauma to their blood vessels causing a rupture, their blood won’t clot properly leading to severe bleeding. This disease is marked by episodes of several bleeding every year, which causes inflammation within the joints, which leads to arthritic and otherwise damaged joints. Currently, the average cost of treatment is about $200,000 a year per patient and involves recombinant protein therapy1. Current Treatment: Recombinant protein therapy is currently the most popular treatment for patients suffering from Hemophilia A and has been very effective at managing the disease. Through multiple injections of recombinant protein Factor VIII, the patients get the much-needed Factor VIII protein. The downside to this technique is that it costs a significant amount of money to administer. Another negative of this therapy is that multiple injections are needed a year, which can become a hassle to the patients receiving treatment. In addition to recombinant protein therapy, Factor VIII can also be obtained from donated blood, but this is less used due to the chance of having a negative immune reaction to the donated blood2. The future treatment of this disease is within the field of gene therapy. Gene therapy Treatment: Gene therapy is an experimental technique that uses genes to treat or prevent diseases through three basic methods: 1. Replacing a mutated gene that causes disease with a healthy copy of the gene. 2. Inactivating or “knocking out” a mutated gene that is functioning improperly. 3. Introducing a new gene into the body to help fight a disease3. The technique currently being applied to Hemophilia A is the third one, in which a new gene is being introduced into the patients that will produce a fully-functioning Factor VIII. Scientists have done many tests on dogs and mice to investigate the actions of their newly created Factor VII gene. In all of the test cases, the animals showed significant improvement and even full recovery. The positives of gene therapy treatment over recombinant protein therapy treatment are the cost and longevity. Gene therapy, once fully developed, will cost patients much less than the recombinant protein therapy. However, the huge advantage of gene therapy is that many fewer injections are required and, in some cases, only one injection could provide life-long production of Factor VIII. The reason for this is because gene therapy corrects the gene that produces Factor VIII (thus allowing it to continuously produce more Factor VIII) instead of just temporarily providing a limited amount of Factor VIII to the patient (as is done with the protein therapy). So how does gene therapy work? Procedure Scientists have recently been using the human immunodeficiency virus (HIV) as a vector to deliver the new Factor VIII gene into the bone marrow of organisms suffering from Hemophilia A. Once the virus has been wiped clean of disease-causing materials, RNA coding for the Factor VIII gene is then inserted into the virus’s genetic material and injected into the organism receiving treatment. Thus, now that the organism has the virus within it, the virus will do what it naturally does and incorporate itself into the host’s DNA. When the organism goes to transcribe and translate the new DNA, it will code for the Factor VIII gene and thus create Factor VIII. Negatives of Gene Therapy Treatment: One initial negative outcome of this procedure was that the newly incorporated Factor VIII gene wasn’t producing enough Factor VIII. However, Scientists have solved this issue by creating a Factor VIII gene that is 90% human and 10% porcine2. It turns out that the porcine Factor VIII is similar enough to human Factor VIII that it’s a viable substitution. Also, porcine Factor VIII produces about 10 times the amount of protein than the human counter-part produces, which solves the quantitative issue of simply the human Factor VIII. Another downside to this therapy is the financial aspect. Clinical human trials are the next step for this treatment, and they are very costly. Also, the recombinant protein Hemophilia treatment industry is a $3.5-4 billion industry and with this new gene therapy treatment it will take a significant financial hit2. This is causing some people to shy away from the new gene therapy treatment, which would cause a loss of business for them. Overall, the gene therapy treatment shows significant increases to the quality of care to patients and is a very viable future option to combat Hemophilia A within humans. Resources: 1. New Gene Therapy Proves Promising as Hemophilia Treatment by Mark Derewicz 2. Gene Therapy and Hemophilia A by www.choa.org 3. What Is Gene Therapy? taken from http://ghr.nlm.nih.gov 4. http://www.wikipedia.org